St Louis: Scientists have linked mutations in a single gene to autism in people
who have a rare tumor syndrome typically diagnosed in childhood.
The findings, in patients with neurofibromatosis type 1 (NF1), may
lead to a better understanding of the genetic roots of autism in the
wider population.
The findings are published Oct. 19 in the journal JAMA Psychiatry.
Studying 531 patients at six clinical centers in the United States,
Belgium, the United Kingdom and Australia, the researchers found that
mutations in the NF1 gene that cause the disease also contributed to autistic behaviors in almost half of the patients.
“NF1 is caused by mutations in a single gene — NF1,” said
first author Stephanie M. Morris, MD, an instructor in neurology. “Our
research indicates that this single gene also is associated with autism
spectrum disorders in these same patients. That may make it possible to
look downstream from the gene to find common pathways that contribute to
autism in the wider population.”
NF1, the disorder caused by NF1 mutations, usually appears
during childhood. Symptoms can vary in severity, but they include café
au lait spots, which are flat, brown spots on the skin. Other symptoms
include tiny nodules on the iris of the eye, nerve tumors, bone
deformities such as a curved spine or a bowed lower leg, and optic
gliomas, tumors of the optic nerve. Kids with NF1 also can have learning
disabilities.
“In the 25-plus years that I’ve taken care of kids with NF1, we’ve
only recently started to recognize that these children also often have
symptoms of autism,” said senior investigator David H. Gutmann, MD, PhD,
the Donald O. Schnuck Family Professor of Neurology and director of the
Washington University NF Center. “In the past, we didn’t really
understand the association between NF1 and autism, but now we have new
insights into the problem, which will allow us to design better
treatments for children with NF1 and autism.”
The findings also could help scientists who study the genetics of
autism understand how mutations in a single gene can contribute to
symptoms of autism, such as problems with social and language skills and
repetitive behaviors.
About 100,000 people in the United States have NF1. It is equally
common in both sexes and in all ethnic groups. Autism, meanwhile,
affects 1 percent to 2 percent of all children in the United States and
is four to five times more common in boys than in girls.
“What’s unique about our findings is that it’s likely mutations in the NF1
gene are driving most of the symptoms of autism in children with NF1,”
said the study’s other senior investigator, John N. Constantino, the
Blanche F. Ittleson Professor of Psychiatry and Pediatrics and director
of the William Greenleaf Eliot Division of Child & Adolescent
Psychiatry. “Here, we have a single-gene disorder that affects a fairly
large number of people and is causing autism in a significant number of
those who are affected. This work could provide us with an opportunity
to study a single gene and figure out what it is doing to cause autistic
syndromes.”
Constantino said most autism spectrum disorders are influenced by
multiple genes but that isolating this one gene can aid efforts to learn
how other, unrelated genes may interact along that same pathway to
contribute to autism in people who don’t have NF1.
Learning how those various genes come together to cause symptoms
eventually could lead to better treatments. But already the findings are
benefiting children and families treated at the Washington University
NF Center.
“We’ve been able to screen children at our center, identify autism
spectrum disorder, attention-deficit disorder and problems with
executive cognitive function,” Morris said. “And when we identify these
deficits in kids, we can tell their parents, inform their schools and
enable these children to get the resources and support they need —
specifically academic and social support – to improve their quality of
life.”